Dynamics of Mitotic Spindle Morphogenesis.

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Cell division is a fundamentally important example of cell behavior. It is based on complex mechanochemical machines consisting of dynamic biopolymers and molecular motors. We focus on one such machine, mitotic spindle, which self-assembles into a bipolar structure from microtubules and multiple motors. Both motors and microtubules generate coordinated forces and movements and govern chromosome separation and intracellular transport. Given this rich repertoire of microtubule and motor functions in the spindle, a current challenge is to understand how the activities of the individual components are coordinated to produce a precision machine capable of segregating chromatids with the fidelity observed in cells. The investigators will use a novel combination of mathematical analysis, computer simulations and experiment to develop explanatory and predictive quantitative models of mitotic spindle. Deterministic and stochastic models will be developed, analyzed and computer simulated. The modeling aims are 1. To analyze the roles of microtubules and multiple motors in spindle morphogenesis, 2. To elucidate mechanisms of self-organization of microtubules and multiple motors into mitotic spindle-like structures, 3. To analyze the roles of microtubules and multiple motors in chromosome positioning, 4. To model interaction between actomyosin contraction and microtubule-motor-dependent transport in cytokinesis. The investigators will use microscopy, genetic and biochemical techniques to obtain data needed to validate the models. Quantitative modeling complemented by experiments will elucidate principles of spatio-temporal organization and regulation of mitotic spindle. The models will allow to test plausible scenarios of mitosis and cell division. They will provide a new interdisciplinary level of understanding and predicting dynamic cell behavior in important biomedical situations.